Long‐term structural and functional consequences of cardiac ischaemia–reperfusion injury in vivo in mice

Abstract

The short-term (<24 h) consequences of oxidative stress induced by ischaemia-reperfusion (IR) have been studied extensively in the mouse heart. However, much less is known about the long-term effects inflicted by a brief ischaemic period on the murine heart. We therefore examined the structural and functional consequences of a 30 min ischaemic period after 2 and 8 weeks of reperfusion and compared these to the effects induced by permanent occlusion of the left anterior descending coronary artery (LAD). The latter procedure resulted in transmural myocardial infarcts of about 52% of the left ventricle. In contrast, the single 30 min ischaemic period led to infarct sizes of about 13% of the left ventricle (range, 4-23%) at 2 and 8 weeks after reperfusion. Maximal cardiac contractility responses (+dP/dt) to dobutamine infusion and volume loading were depressed at 2, but not at 8 weeks after IR. The restoration of cardiac contractility at 8 weeks after IR was associated with a significant 20% enlargement of the end-diastolic volume and 16% increase of the left ventricular wall thickness. These changes in cardiac geometry were less pronounced at 2 weeks after IR. Histological examination revealed that the IR injury was associated with prominent calcification. At 2 and at 8 weeks after IR, 25 ± 5 and 38 ± 5% of the injured area was calcified as observed in 69 and 73% of the animals, respectively. After permanent occlusion of the LAD, calcification was not observed and healing of the affected area was characterized by thinning and dilatation of the infarcted myocardium. These data indicate that, in mice, a single 30 min period of ischaemia reduced ventricular contractility up to at least 2 weeks after reperfusion. However, 8 weeks after IR, cardiac function was restored by eccentric hypertrophy associated with calcification of the injured ventricular wall.

Neuroprotective antioxidant STAZN protects against myocardial ischemia/reperfusion injury

“…This may reflect compensatory ventricular hypertrophy. Myocyte hypertrophy has been described as early as 3 days after infarction in coronary artery ligation models [41] and can be seen within 2-3 weeks after onset of hemodynamic loading in mouse and rat models of myocardial ischemia-reperfusion injury [42,43]. Hypertrophy is a major element of ventricular remodeling after MI, and a frequent precursor of congestive heart failure.…”

Characterization of the structural and functional changes in the myocardium following focal ischemia-reperfusion injury

“…However, the enlargement of EDV and the relative thickening of remote regions of LV suggest an eccentric hypertrophic response to I/R injury. De Celle et al (6) studied LV remodeling in mice until 8-wk post-I/R and also reported a positive correlation between infarct size and ventricular weight. This long-term remodeling response can be explained as a compensatory mechanism for reduced cardiac contractility caused by time-dependent functional and structural damage caused by I/R.…”

Preemptive heme oxygenase-1 gene delivery reveals reduced mortality and preservation of left ventricular function 1 yr after acute myocardial infarction

“…In contrast to the permanent ligation model of MI, which induces rapid thinning of the infarcted LV wall and chamber dilatation, the I/R model of MI leads to slow-developing LV remodeling that is generally complete by 3-6 mo and recapitulates some features of LV remodeling in humans with reperfused MI (3,11,26). The results for echocardiographic analysis at 2 wk in the LacZ (n ϭ 5)-and HO-1 (n ϭ 5)-treated animals are shown in Fig.…”